Mini-brains reveal how Zika causes damage in fetuses

US researchers said Friday they successfully created inexpensive mini-brains in lab to reveal how the Zika virus causes microcephaly and other damage in fetuses.

The study, led by Guo-li Ming and Hongjun Song at the Johns Hopkins University and published in the U.S. journal Cell, supported that the mosquito-borne virus prefers to infect neural stem cells but the extent of damage differs depending on time of infection.

The results confirmed what almost the same team suspected in earlier experiments done in two-dimensional tissue cultures.

Mini-brains, or brain-region-specific organoids, have been actively used in research for years, but they are limited by their high cost, lack of access for most labs, and tricky protocols that prevent clear control experiments.

The Hopkins group solved these problems by 3D printing so-called miniaturized spinning bioreactors to mass produce mini-brains from human stem cells, which can mimic the front, middle and back of a human brain.

These mini-brains can survive and grow for up to six months, thereby allowing the researchers to induce Zika infection during developmental stages equivalent to very early and mid-pregnancy.

The 3D experiments replicated the team's previous work finding that the virus prefers to infect neural stem cells and supported clinical findings that the developing brain is most at risk during the first trimester, or first three months, of pregnancy.

"If infection occurred very early in development, the virus mostly infected the mini-brains' neural progenitor cells, and the effects were very severe," said Ming. "After a while, the mini-brains would stop growing and disintegrate."

"At a later stage, mimicking the second trimester, Zika still preferentially infected neural progenitor cells, but it also affected some neurons. Growth was slower, and the cortex was thinner than in noninfected brains."

These different effects correspond to what clinicians have seen in infants born to women who contracted Zika during pregnancy, as well as miscarriages, she noted, namely that the earlier in pregnancy Zika infection occurs, the more severe its effects.

The research group's next step will be to test drugs using the mini-brains to see whether one might provide some protection against Zika.